The Promotion of Physical Activity for the Prevention of Alzheimer's Disease in Adults with Down Syndrome

摘要 居住在美国的唐氏综合症 (DS) 患者人数已从约 50,000 人增加到约 250,700 人 过去70年几乎所有 DS 患者都表现出与阿尔茨海默病 (AD) 相关的病理学特征 早在 30 岁就开始了。之前对典型发育成年人的研究表明， 中度至剧烈体力活动（MVPA）可以改善认知功能并预防与年龄相关的 大脑结构和功能的变化；然而，增加 MVPA 对 尚未评估患有 DS 的成人的 AD 发展情况。尽管 MVPA 对 认知和 AD 风险，患有 DS 的年轻人参与 MVPA 的比例较低。研究有限 评估增加 DS 成人 MVPA 的策略，但未能成功增加短期 期限（≤ 12 周）或长期 MVPA（12 个月）。我们的初步调查结果（12 周） 在训练有素的健康教练的指导下，远程向家中患有 DS 的成年人群体提供实时 MVPA (n=27)，通过平板电脑上的视频会议表现出高出席率，期间 MVPA 增加 小组会议，以及认知功能的改善。然而，可持续性对每日总量的影响 MVPA、最佳会话频率以及远程认知功能和大脑健康的潜在影响 在患有 DS 的成人中进行的团体 MVPA 课程尚不清楚。因此，我们建议 12 个月。早期阶段 对 80 名患有 DS 的非痴呆成人进行的临床试验，以确定远程治疗的可行性和潜在功效 提供小组 MVPA 课程，以相对于常规护理对照增加每日 MVPA。参加者将是 随机参加低频率的 40 分钟远程小组 MVPA 会议（每周 1 次会议，RL）， 高频率（每周 3 次，RH），或常规护理控制。 RL 和 RH 组的内容将是 除了小组会议频率（每周 1 次与 3 次）之外，其他均相同。与资金一致 公告 PAR-18-877 该试验将评估 RL、RH 和 UC 对 MVPA 进行干预，并收集 MVPA 对认知和测量影响的初步估计 DS 成人患者的大脑健康与 AD 相关。需要此信息来通知开发 充分有力的后期验证性试验，以评估增加 MVPA 预防或延迟的作用 患有 DS 的成人患有 AD。我们的主要目标是评估基线时 RL、RH 和 UC 组的每日 MVPA（分钟）， 3、6、9 和 12 个月，并获得 12 个月内 MVPA 变化的效应大小。次要目标 1 将评估 MVPA 对 RL、RH 和 UC 臂对心血管健康、生活质量、认知能力的影响 与 AD 相关的功能和大脑参数（整体和局部脑容量、功能连接性、静息状态） 状态 MRI、脑血流）在基线、6 个月和 12 个月时。次要目标2将确定可行性 RL、RH 和 UC 组的保留、会议出席率、录制会议的使用（仅限 RH/RL）和安全性。

Abstract The number of people with Down syndrome (DS) living the U.S. has grown from ~50,000 to ~250,700 over the past 70 yrs. Nearly all individuals with DS display pathology associated with Alzheimer's disease (AD) beginning as early as age 30. Previous research in typically developed adults suggests that increased moderate-to-vigorous physical activity (MVPA) may improve cognitive function and protect against age-related structural and functional changes in the brain; however, the potential impact of increased MVPA on the development of AD in adults with DS has not been evaluated. Despite the potential positive impact of MVPA on cognition and AD risk, participation in MVPA among young adults with DS is low. The limited research evaluating strategies for increasing MVPA in adults with DS and has been unsuccessful in increasing short- term (≤ 12 wks.) or long-term MVPA (12 mo.). Results from our preliminary investigation (12 wks.) which remotely delivers real-time MVPA, led by a trained health coach, to groups of adults with DS in their homes (n=27), via video conferencing on a tablet computer demonstrated high attendance, increased MVPA during group sessions, and improvements in cognitive function. However, the sustainability, impact on total daily MVPA, optimal session frequency, and potential impacts on cognitive function and brain health of remotely delivered group MVPA sessions in adults with DS are unknown. Therefore, we propose a 12 mo. early stage clinical trial in 80 non-demented adults with DS to determine the feasibility and potential efficacy of remotely delivered group MVPA sessions to increase daily MVPA, relative to a usual care control. Participants will be randomized to attend 40 min remotely delivered group MVPA sessions at a low frequency (1 session/wk.,RL), high frequency (3 sessions/wk., RH), or usual care control. Content for both the RL and RH arms will be identical with the exception of group session frequency (1 vs. 3/wk.). Consistent with the funding announcement PAR-18-877 this trial will assess the feasibility and potential effectiveness of the RL, RH, and UC interventions on MVPA, and gather initial estimates of the impact of MVPA on cognition and measure of brain health related to AD in adults with DS. This information is required to inform the development of adequately powered, late stage confirmatory trials to evaluate the role of increased MVPA to prevent or delay AD in adults with DS. Our primary aim will assess daily MVPA (min) in the RL, RH, and UC arms at baseline, 3, 6, 9, and 12 mos., and obtain effect sizes for change in MVPA over 12-mos. Secondary aim 1 will assess the impact of MVPA across the RL, RH, and UC arms on cardiovascular fitness, quality of life, cognitive function and brain parameters related to AD (whole and regional brain volume, functional connectivity, resting state MRI, cerebral blood flow) at baseline, 6, and 12 mos. Secondary aim 2 will determine the feasibility (retention, session attendance, use of recorded sessions (RH/RL only) and safety) of RL, RH, and UC arms.